Methods of treating TTR amyloidosis using AG10

Abstract

Described herein are methods for treating transthyretin (TTR) amyloidosis in a subject. The methods include specific dosing regimens that have great efficacy in treating the subjects and that are well tolerated in subjects.

What is claimed is: 
     
       1. A method of treating transthyretin (TTR) amyloidosis in a subject in need thereof, the method comprising orally administering to a subject in need thereof a total daily dosage of about 1,600 mg of Compound 1, having the formula: 
       
         
           
           
               
               
           
         
         in HCl salt form, wherein Compound 1 is administered twice daily. 
       
     
     
       2. The method of  claim 1 , wherein said TTR amyloidosis is a disease or condition selected from the group consisting of familial amyloid polyneuropathy, familial amyloid cardiomyopathy, senile systemic amyloidosis, central amyloidosis, ocular amyloidosis, Leptomeningeal amyloidosis, oculoleptomeningeal amyloidosis, vitreous amyloidosis, gastrointestinal amyloidosis, neuropathic amyloidosis, non-neuropathic amyloidosis, non-hereditary amyloidosis, reactive/secondary amyloidosis, cerebral amyloidosis. 
     
     
       3. The method of  claim 1 , wherein said TTR amyloidosis is transthyretin amyloidosis (ATTR) cardiomyopathy. 
     
     
       4. The method of  claim 1 , wherein said TTR amyloidosis is transthyretin amyloidosis (ATTR) polyneuropathy. 
     
     
       5. The method of  claim 3 , wherein administration of a therapeutically effective amount of Compound 1 in a subject with ATTR cardiomyopathy improves the subject's performance in a six minute walk test as compared to subjects not receiving treatment. 
     
     
       6. The method of  claim 3 , wherein administration of a therapeutically effective amount of Compound 1 in a subject with ATTR cardiomyopathy decreases the frequency of cardiovascular-related hospitalizations as compared to subjects not receiving treatment. 
     
     
       7. The method of  claim 3 , wherein administration of a therapeutically effective amount of Compound 1 in a subject with ATTR cardiomyopathy decreases mortality as compared to subjects not receiving treatment. 
     
     
       8. The method of  claim 4 , wherein administration of a therapeutically effective amount of Compound 1 in a subject with ATTR polyneuropathy improves the Neuropathy Impairment Score (NIS) in said subject. 
     
     
       9. The method of  claim 3 , wherein said ATTR cardiomyopathy is wild-type ATTR cardiomyopathy (ATTRwt-CM). 
     
     
       10. The method of  claim 3 , wherein said ATTR cardiomyopathy is familial ATTR cardiomyopathy (ATTRm-CM). 
     
     
       11. The method of  claim 4 , wherein said ATTR polyneuropathy is wild-type ATTR polyneuropathy (ATTRwt-PN). 
     
     
       12. The method of  claim 4 , wherein said ATTR polyneuropathy is familial ATTR polyneuropathy (ATTRm-PN). 
     
     
       13. The method of  claim 1 , wherein administration of a therapeutically effective amount of Compound 1 increases transthyretin (TTR) blood serum concentration relative to a baseline level. 
     
     
       14. The method of  claim 1 , wherein administration of a therapeutically effective amount of Compound 1 increases transthyretin (TTR) blood serum concentration by at least 10% relative to a baseline level after 28 days of treatment.